The goal of our research program is to understand the causes and underlying mechanisms of amblyopia. Our systemmatic comparisons of animal models of deprivation (monocular, binocular) and non-deprivation (strabismic) amblyopia have revealed significant differences between the two etiologies in terms of physiological and behavioral deficits. It appears that two independent processes are involved in amblyopia, one related to binocular competition and another related to abnormal stimulation per se. These two processes occur to different extents in deprivation and non-deprivation amblyopia and the major deficits in non-deprivation amblyopia appear to result from abnormal stimulation. In the present proposal we will extend these results in several new directions. One will be to more precisely specify the environmental cause of non-deprivation amblyopia. In these studies, we will directly explore the role of preferential eye usage and the role of a defocused image in the strabismic eye in producing physiological deficits in single cells in visual cortex (VC) and the lateral geniculate nucleus (LGN). A second aim will be to assess the role of anatomical loss in the geniculo-cortical pathway (as indicated by transynaptic autoradiography) - in producing physiological deficits in VC and LGN. These studies will use several new animal models which will allow us to more directly define the relation between structural and functional deficits. Our final aim will be to directly assess the relationship between different physiological deficits in VC and LGN and the severity of behavioral amblyopic deficits (as indicated by contrast sensitivity). These studies will significantly improve our understanding not only of the underlying mechanisms of amblyopia but also better define the etiological basis of th disorder with paradigms that are directly applicable to clinical management.